19-45368348-T-C

Position:

• chr19-45368348-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000400.4(ERCC2):​c.360+282A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 151,992 control chromosomes in the GnomAD database, including 32,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.64 (32685 hom., cov: 31)
• Consequence: ERCC2 NM_000400.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.20

Genes affected

ERCC2 (HGNC:3434): (ERCC excision repair 2, TFIIH core complex helicase subunit) The nucleotide excision repair pathway is a mechanism to repair damage to DNA. The protein encoded by this gene is involved in transcription-coupled nucleotide excision repair and is an integral member of the basal transcription factor BTF2/TFIIH complex. The gene product has ATP-dependent DNA helicase activity and belongs to the RAD3/XPD subfamily of helicases. Defects in this gene can result in three different disorders, the cancer-prone syndrome xeroderma pigmentosum complementation group D, trichothiodystrophy, and Cockayne syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

ERCC2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-45368348-T-C is Benign according to our data. Variant chr19-45368348-T-C is described in ClinVar as [Benign]. Clinvar id is 1294042.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC2	NM_000400.4	c.360+282A>G		intron_variant		ENST00000391945.10	NP_000391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC2	ENST00000391945.10	c.360+282A>G		intron_variant		1	NM_000400.4	ENSP00000375809.4

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97028 AN: 151874 Hom.: 32634 Cov.: 31

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.594

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.639 AC: 97131 AN: 151992 Hom.: 32685 Cov.: 31 AF XY: 0.636 AC XY: 47232 AN XY: 74280

Gnomad4 AFR AF: 0.870

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.594

Alfa AF: 0.565 Hom.: 33060

Bravo AF: 0.646

Asia WGS AF: 0.566 AC: 1971 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.29
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1618536; hg19: chr19-45871606;